scholarly journals Exceptional Nuclease Resistance of Paranemic Crossover (PX) DNA and Crossover-Dependent Biostability of DNA Motifs

2020 ◽  
Vol 142 (14) ◽  
pp. 6814-6821 ◽  
Author(s):  
Arun Richard Chandrasekaran ◽  
Javier Vilcapoma ◽  
Paromita Dey ◽  
Siu Wah Wong-Deyrup ◽  
Bijan K. Dey ◽  
...  
Keyword(s):  
Dna Motifs ◽  
Nuclease Resistance ◽  
Paranemic Crossover

Facilitation of DNA self-assembly by relieving the torsional strains between building blocks

2017 ◽  
Vol 15 (2) ◽  
pp. 465-469 ◽  
Author(s):  
Weili Shen ◽  
Qing Liu ◽  
Baoquan Ding ◽  
Changqing Zhu ◽  
Zhiyong Shen ◽  
...  
Keyword(s):  
Self Assembly ◽  
Building Blocks ◽  
Base Pairs ◽  
Dna Motifs ◽  
Torsional Strain ◽  
High Uniformity ◽  
Self Assembled ◽  
Paranemic Crossover

Overwound and underwound paranemic crossover (PX) DNA motifs have been self-assembled to generate high uniformity lattices, by adjusting the number of base pairs in the JX region adjacent to the PX structure to relieve torsional strain.

scholarly journals Exceptional biostability of paranemic crossover (PX) DNA, crossover-dependent nuclease resistance, and implications for DNA nanotechnology

2019 ◽  
Author(s):  
Arun Richard Chandrasekaran ◽  
Javier Vilcapoma ◽  
Paromita Dey ◽  
SiuWah Wong-Deyrup ◽  
Bijan K. Dey ◽  
...  
Keyword(s):  
Biomedical Applications ◽  
Biological Fluids ◽  
Dna Nanotechnology ◽  
Full Potential ◽  
Dna Nanostructures ◽  
Double Stranded Dna ◽  
Nuclease Resistance ◽  
Order Of Magnitude ◽  
Paranemic Crossover ◽  
The Many

AbstractInherent nanometer-sized features and molecular recognition properties make DNA a useful material in constructing nanoscale objects, with alluring applications in biosensing and drug delivery. However, DNA can be easily degraded by nucleases present in biological fluids, posing a considerable roadblock to realizing the full potential of DNA nanotechnology for biomedical applications. Here we investigated the nuclease resistance and biostability of the multi-stranded motif called paranemic crossover (PX) DNA and discovered a remarkable and previously unreported resistance to nucleases. We show that PX DNA has more than an order of magnitude increased resistance to degradation by DNase I, serum, and urine compared to double stranded DNA. We further demonstrate that the degradation resistance decreases monotonically as DNA crossovers are removed from the structure, suggesting that frequent DNA crossovers disrupt either the binding or catalysis of nucleases or both. Further, we show using mouse and human cell lines that PX DNA does not affect cell proliferation or interfere with biological processes such as myogenesis. These results have important implications for building DNA nanostructures with enhanced biostability, either by adopting PX-based architectures or by carefully engineering crossovers. We contend that such crossover-dependent nuclease resistance could potentially be used to add “tunable biostability” to the many features of DNA nanotechnology.

scholarly journals CpGmotifs: a tool to discover DNA motifs associated to CpG methylation events

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Giovanni Scala ◽  
Antonio Federico ◽  
Dario Greco
Keyword(s):  
Dna Methylation ◽  
Motif Discovery ◽  
Cpg Methylation ◽  
Functional Interpretation ◽  
Dna Motifs ◽  
Molecular Alterations ◽  
Link Type ◽  
Dna Motif ◽  
Quantitative Manner ◽  
Dna Motif Discovery

Abstract Background The investigation of molecular alterations associated with the conservation and variation of DNA methylation in eukaryotes is gaining interest in the biomedical research community. Among the different determinants of methylation stability, the DNA composition of the CpG surrounding regions has been shown to have a crucial role in the maintenance and establishment of methylation statuses. This aspect has been previously characterized in a quantitative manner by inspecting the nucleotidic composition in the region. Research in this field still lacks a qualitative perspective, linked to the identification of certain sequences (or DNA motifs) related to particular DNA methylation phenomena. Results Here we present a novel computational strategy based on short DNA motif discovery in order to characterize sequence patterns related to aberrant CpG methylation events. We provide our framework as a user-friendly, shiny-based application, CpGmotifs, to easily retrieve and characterize DNA patterns related to CpG methylation in the human genome. Our tool supports the functional interpretation of deregulated methylation events by predicting transcription factors binding sites (TFBS) encompassing the identified motifs. Conclusions CpGmotifs is an open source software. Its source code is available on GitHub https://github.com/Greco-Lab/CpGmotifs and a ready-to-use docker image is provided on DockerHub at https://hub.docker.com/r/grecolab/cpgmotifs.

scholarly journals Comprehensive discovery of DNA motifs in 349 human cells and tissues reveals new features of motifs

2014 ◽  
Vol 43 (1) ◽  
pp. 74-83 ◽  
Author(s):  
Yiyu Zheng ◽  
Xiaoman Li ◽  
Haiyan Hu
Keyword(s):  
Human Cells ◽  
Dna Motifs

scholarly journals Conformation and protein interactions of intramolecular DNA and phosphorothioate four-way junctions

2020 ◽  
pp. 153537022097397
Author(s):  
Maria Troisi ◽  
Mitchell Klein ◽  
Andrew C Smith ◽  
Gaston Moorhead ◽  
Yonatan Kebede ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Therapeutic Potential ◽  
Dnase I ◽  
Protein Recognition ◽  
Exonuclease Iii ◽  
Branched Dna ◽  
Acid Cleavage ◽  
Nuclease Digestion ◽  
Nuclease Resistance ◽  
Exo Iii

The objectives of this study are to evaluate the structure and protein recognition features of branched DNA four-way junctions in an effort to explore the therapeutic potential of these molecules. The classic immobile DNA 4WJ, J1, is used as a matrix to design novel intramolecular junctions including natural and phosphorothioate bonds. Here we have inserted H2-type mini-hairpins into the helical termini of the arms of J1 to generate four novel intramolecular four-way junctions. Hairpins are inserted to reduce end fraying and effectively eliminate potential nuclease binding sites. We compare the structure and protein recognition features of J1 with four intramolecular four-way junctions: i-J1, i-J1(PS1), i-J1(PS2) and i-J1(PS3). Circular dichroism studies suggest that the secondary structure of each intramolecular 4WJ is composed predominantly of B-form helices. Thermal unfolding studies indicate that intramolecular four-way junctions are significantly more stable than J1. The Tm values of the hairpin four-way junctions are 25.2° to 32.2°C higher than the control, J1. With respect to protein recognition, gel shift assays reveal that the DNA-binding proteins HMGBb1 and HMGB1 bind the hairpin four-way junctions with affinity levels similar to control, J1. To evaluate nuclease resistance, four-way junctions are incubated with DNase I, exonuclease III (Exo III) and T5 exonuclease (T5 Exo). The enzymes probe nucleic acid cleavage that occurs non-specifically (DNase I) and in a 5ʹ→3ʹ (T5 Exo) and 3ʹ→5ʹ direction (Exo III). The nuclease digestion assays clearly show that the intramolecular four-way junctions possess significantly higher nuclease resistance than the control, J1.

scholarly journals The Arabidopsis GAGA-Binding Factor BASIC PENTACYSTEINE6 Recruits the POLYCOMB-REPRESSIVE COMPLEX1 Component LIKE HETEROCHROMATIN PROTEIN1 to GAGA DNA Motifs

2015 ◽  
Vol 168 (3) ◽  
pp. 1013-1024 ◽  
Author(s):  
Andreas Hecker ◽  
Luise H. Brand ◽  
Sébastien Peter ◽  
Nathalie Simoncello ◽  
Joachim Kilian ◽  
...  
Keyword(s):  
Dna Motifs ◽  
Binding Factor

Predicting DNA Motifs by Using Evolutionary Multiobjective Optimization

2012 ◽  
Vol 42 (6) ◽  
pp. 913-925 ◽  
Author(s):  
D. L. Gonzalez-Álvarez ◽  
M. A. Vega-Rodriguez ◽  
J. A. Gomez-Pulido ◽  
J. M. Sanchez-Pérez
Keyword(s):  
Multiobjective Optimization ◽  
Dna Motifs ◽  
Evolutionary Multiobjective Optimization

scholarly journals Discovering human transcription factor interactions with genetic variants, novel DNA motifs, and repetitive elements using enhanced yeast one-hybrid assays

2018 ◽  
Author(s):  
Shaleen Shrestha ◽  
Jared Allan Sewell ◽  
Clarissa Stephanie Santoso ◽  
Elena Forchielli ◽  
Sebastian Carrasco Pro ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Hormone Receptors ◽  
Single Nucleotide Variants ◽  
Alu Elements ◽  
Dna Motifs ◽  
Super Enhancer ◽  
Dna Elements ◽  
Genomic Regions ◽  
Factor Interactions ◽  
Ets Factors

ABSTRACTIdentifying transcription factor (TF) binding to noncoding variants, uncharacterized DNA motifs, and repetitive genomic elements has been technically and computationally challenging. Current experimental methods, such as chromatin immunoprecipitation, generally test one TF at a time, and computational motif algorithms often lead to false positive and negative predictions. To address these limitations, we developed two approaches based on enhanced yeast one-hybrid assays. The first approach interrogates the binding of >1,000 human TFs to repetitive DNA elements, while the second evaluates TF binding to single nucleotide variants, short insertions and deletions (indels), and novel DNA motifs. Using the first approach, we detected the binding of 75 TFs, including several nuclear hormone receptors and ETS factors, to the highly repetitive Alu elements. Using the second approach, we identified cancer-associated changes in TF binding, including gain of interactions involving ETS TFs and loss of interactions involving KLF TFs to different mutations in the TERT promoter, and gain of a MYB interaction with an 18 bp indel in the TAL1 super-enhancer. Additionally, we identified the TFs that bind to three uncharacterized DNA motifs identified in DNase footprinting assays. We anticipate that these approaches will expand our capabilities to study genetic variation and under-characterized genomic regions.

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